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Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in Old Order Amish

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Abstract

Aims/hypothesis

SLC30A8 encodes a zinc transporter in the beta cell; individuals with a common missense variant (rs13266634; R325W) in SLC30A8 demonstrate a lower early insulin response to glucose and an increased risk of type 2 diabetes. We hypothesised that zinc supplementation may improve insulin secretion in a genotype-dependent manner.

Methods

We evaluated the early insulin response to glucose (using frequently sampled intravenous glucose tolerance testing) by R325W genotype before and after 14 days of supplementation with oral zinc acetate (50 mg elemental zinc) twice daily in healthy non-diabetic Amish individuals (N = 55).

Results

Individuals with RW/WW genotypes (n = 32) had the lowest insulin response to glucose at 5 and 10 min at baseline (vs RR homozygotes [n = 23]). After zinc supplementation, the RW/WW group experienced 15% and 14% increases in the insulin response to glucose at 5 and 10 min, respectively (p ≤ 0.04), and, compared with RR homozygotes, experienced a 26% (p = 0.04) increase in insulin at 5 min. We observed reciprocal decreases in proinsulin:insulin in the RW/WW (p = 0.002) vs RR group (p = 0.048), suggesting a genotype-specific improvement in insulin processing.

Conclusions/interpretation

Zinc supplementation appears to affect the early insulin response to glucose differentially by rs13266634 genotype and could be beneficial for diabetes prevention and/or treatment for some individuals based on SLC30A8 variation.

Trial registration: ClinicalTrials.gov NCT00981448

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Abbreviations

FS-IVGTT:

Frequently sampled IVGTT

HOMA-IR:

HOMA of insulin resistance

SNP:

Single nucleotide polymorphism

ZnT8:

Zinc transporter protein member 8

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Acknowledgements

The authors thank G. Brewer (University of Michigan, Ann Arbor, MI, USA) for his advice on the measurement of zinc in this study. The authors thank B. Mitchell and K. Ryan (University of Maryland School of Medicine, Baltimore, MD, USA) for their assistance with analyses. The authors are grateful to the Zinc Insulin Pharmacogenetics study participants and staff at the Amish Research Clinic in Lancaster, PA, USA (University of Maryland School of Medicine).

Funding

This research was supported in part by the Mid-Atlantic Nutrition Obesity Research Center, P30 DK072488, from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and by The Johns Hopkins Clinical Research Scholars Program (1KL2 RR025006).

Duality of interest

The authors have no conflicts of interest to disclose. Adeona Pharmaceuticals (Ann Arbor, MI, USA) provided measurement of serum zinc free of charge.

Contribution statement

NMM refined the study design, collected and interpreted the data, and drafted and revised the manuscript. MF collected and interpreted the data, contributed to the methods of the manuscript and reviewed/edited the manuscript. JMC refined the study design, interpreted the data and reviewed/edited the manuscript. ARS refined the study design, collected and interpreted the data and reviewed/edited the manuscript. WHLK interpreted the data and reviewed/edited the manuscript. All authors approved the final version of the paper except for WHLK, who died before she was able to do so. NMM takes responsibility for the contents of this article.

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Authors and Affiliations

  1. Division of General Internal Medicine, Johns Hopkins University School of Medicine, 2024 E. Monument Street, Suite 2-600, Baltimore, MD, 21287, USA

    Nisa M. Maruthur, Jeanne M. Clark & W. H. Linda Kao

  2. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    Nisa M. Maruthur, Jeanne M. Clark & W. H. Linda Kao

  3. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA

    Nisa M. Maruthur, Jeanne M. Clark & W. H. Linda Kao

  4. Program for Personalized and Genomic Medicine, Metabolism and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Mao Fu & Alan R. Shuldiner

  5. Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Mao Fu & Alan R. Shuldiner

  6. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USA

    Alan R. Shuldiner

Authors
  1. Nisa M. Maruthur
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  2. Jeanne M. Clark
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  3. Mao Fu
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  4. W. H. Linda Kao
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  5. Alan R. Shuldiner
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Correspondence to Nisa M. Maruthur.

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Maruthur, N.M., Clark, J.M., Fu, M. et al. Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in Old Order Amish. Diabetologia 58, 295–303 (2015). https://doi.org/10.1007/s00125-014-3419-1

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  • DOI: https://doi.org/10.1007/s00125-014-3419-1

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